CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.
Clin Pharmacol Ther
; 95(2): 216-27, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24060820
ABSTRACT
The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Neoplasias da Mama
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Antineoplásicos Hormonais
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Citocromo P-450 CYP2D6
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article